News Scan for Oct 28, 2022

News brief

Study: 30% of COVID patients had rebound after 2 days without symptoms

Nearly one third of 158 untreated COVID-19 patients experienced symptom rebound after being symptom-free for at least 2 consecutive days, finds a study of US adults published yesterday in JAMA Network Open.

A team led by researchers from the University of California at San Diego and Harvard University investigated whether the symptom rebound often attributed to treatment with the antiviral drug nirmatrelvir-ritonavir (Paxlovid) is simply part of the natural course of some COVID-19 cases.

The researchers said that the biological underpinning of COVID-19 rebound after Paxlovid treatment is unclear but may include rapid clearance of nirmatrelvir, delayed immune responses, or the development of drug resistance. Study participants completed a daily diary of 13 symptoms for 28 days in 2020. Median patient age was 47 years, and median time from symptom onset to enrollment was 6 days.

During follow-up, 68% of patients reported symptom resolution, of which 44% (30% of all participants) later reported recurrence of at least 1 of the 13 symptoms. Eighty-five percent said their symptoms were mild, and 15% reported at least one moderate symptom.

The most common rebound symptoms were cough (44%), fatigue (35%), and headache (35%), similar to those reported at enrollment (except that pain and aches were reported more often at enrollment), and to those of patients who still had symptoms at the end of the study. Eight patients (5%) were hospitalized, but none died.

The researchers cautioned that the study was conducted before COVID-19 vaccines became available and during periods dominated by wild-type SARS-CoV-2 and the Alpha variant and thus may not be generalizable to current conditions.

"We found the natural history of untreated COVID-19 was variable and undulating," the authors wrote, adding that rebound symptoms are not predictive of severe disease. "Our observed variation may explain some of the rebound of symptoms after treatment for COVID-19, like in cases of what has been described as Paxlovid rebound."
Oct 27 JAMA Netw Open research letter

COVID-19 vaccines linked to lower ICU admissions for pneumonia

A new study in JAMA Network Open based on Italian intensive care unit (ICU) admissions shows that COVID-19 vaccination was tied to lower rates of ICU admissions due to pneumonia but was not associated with a reduction in hospital mortality.

The cohort study was based on vaccine records of 10 million residents of the Lombardy region of Italy from Aug 1 to Dec 15, 2021. The median age was 48, and 51% of residents were female. As of Jan 31, 2022, a total of 7,863,417 residents were vaccinated; 79.5%; received an mRNA vaccine, 7.0%; received an adenoviral vector vaccine (AdV), 13.5% received a mix of vaccines, and 57.2% were boosted.

There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period, of whom 139 (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Adjusting for age, sex, time from the last administered dose, and vaccine type, the risk of ICU admission remained lower in vaccinated individuals compared with those unvaccinated, the authors said.

The lowest incident rate ratios (IRRs) (0.03; 95% confidence interval [CI], 0.03 to 0.04; P < .001) were among individuals who had received an mRNA vaccine within 120 days and translate to 97% protection from ICU illness. The highest IRR (0.21; 95% CI, 0.19 to 0.24; P < .001), or 79% protection, was among individuals who had a time from the last administered dose of an AdV vaccine of more than 120 days.

"Even 4 months after vaccine administration, vaccinated individuals still had a 4.5-times lower risk of ICU admission compared with unvaccinated individuals. Furthermore, mRNA vaccines maintained a greater and more prolonged effectiveness in preventing ICU admission compared with AdV," the authors wrote.

Hospital mortality rates were not, however, significantly affected by vaccination status, with crude mortality rates ranging from 23% to 33% for vaccinated patients and 22% and 29% for unvaccinated patient. The authors said this was likely due to advanced patient age and comorbidities.
Oct 27 JAMA Netw Open study

CDC reports more flu rises, first pediatric death of the season

US flu activity continued its early rise last week, with the first pediatric flu death of the new season reported and hospitalization rates already rising, the Centers for Disease Control and Prevention (CDC) said today in its weekly update.

The pediatric flu death involved an H3N2 virus and occurred during the week that ended on Oct 8. The CDC said the cumulative hospitalization rate for flu last week was 1.5 per 100,000 population, which is at the highest level for this point of the season since 2010-11. More than 94% of flu hospitalizations involved influenza A, and of subtyped samples, 72.9% were the H3N2 strain. Rates were highest in seniors and in children up to age 4 years.

Other markers that the CDC uses to track flu activity also rose, including the percentage of outpatient visits for flu, a measure that can also reflect activity from other respiratory viruses that have similar symptoms.

The southeast and south-central regions are still reporting the highest flu levels. The percentage of respiratory samples that tested positive for flu increased last week in most parts of the country, to 6.2% overall.

The CDC recommends that everyone age 6 months and older receive a flu vaccine, which it says is the best way to protect against flu and serious outcomes in people with are vaccinated but still get sick. This year, federal health officials have urged the public to get vaccinated against flu at the same time they receive updated COVID-19 boosters.
Oct 28 CDC FluView update

Three countries report new polio cases

Three countries have new polio cases this week, all vaccine-derived types. The Democratic Republic of the Congo (DRC), Niger, and Nigeria all recorded new cases, according to the weekly report published by the Global Polio Eradication Initiative (GPEI).

Niger and Nigeria each reported a single case of circulating vaccine-derived poliovirus type 2 (cVDPV2). In Niger the case was reported in Maradi. There are now 11 cases in 2022, and 18 were reported in 2021.

Nigeria's case was recorded in Borno, raising the yearly total to 37 cases. There were 415 cases reported in 2021.

The DRC is intensifying its outbreak response as one case of circulating vaccine-derived poliovirus type 1 (cVDPV1) was reported in Haut Lomami. There are now 29 cases reported in 2022. Six new cases of cVDPV2 were reported, bringing the number of such cases reported in 2022 to 160. The country had 28 cVDPV2 cases in 2021.
Oct 28 GPEI report

Stewardship / Resistance Scan for Oct 28, 2022

News brief

**Poor outcomes seen in those with resistant E coli bloodstream infections**

An analysis of patients with Escherichia coli bloodstream infections (BSIs) found notably poorer outcomes in those with ceftriaxone-resistant infections, US researchers reported yesterday in Open Forum Infectious Diseases.

For the multicenter prospective cohort study, researchers with the Antibacterial Resistance Leadership Group analyzed data on adult and pediatric patients with E coli BSIs at 14 US hospitals from Nov 12, 2020, to Apr 18, 2021. For each patient with a ceftriaxone-resistant (CRO-R) E coli BSI who was enrolled, the next consecutive patient with ceftriaxone-susceptible E coli BSI was included. The primary outcome was the desirability of outcome ranking (DOOR) at day 30 after collection of index culture, which the study authors say they chose because it captures a more wide-ranging experience of patients infected with drug-resistant pathogens.

A total of 300 patients (median age, 68 years) were included in the analysis, with 150 in the CRO-R group and 150 in the CRO-S group. Patients with CRO-R infections had more overall comorbidities than those with CRO-S infections. In the unadjusted DOOR analysis, there was a 58% probability of a worse clinical outcome in patients with CRO-R E coli BSI versus a CRO-S E coli BSI. No difference was observed in the inverse probability weighting analysis, which was used to reduce confounding and found a 54% probability of a worse outcome in patients with CRO-R infections.

Although the difference in mortality between the two groups was not statistically significant, patients with CRO-R E coli BSI were almost more likely to have longer hospital stays (8 vs 6 days), to remain in the hospital at day 30 (10% vs 4%), and to be transferred to long-term care facilities (22% vs 12%) than those with CRO-S infections.

"These findings underscore the importance of judicious antibiotic use to reduce the development of antibiotic resistance and its subsequent negative impacts 9 on patient outcomes," the study authors wrote.

Oct 27 Open Forum Infect Dis abstract

Study highlights inappropriate pediatric antibiotic use in China

A study of outpatient antibiotic prescribing at primary care institutions in southwest China found that more than 80% of prescriptions for children in 2020 were inappropriate, researchers reported this week in BMC Primary Care.

Using electronic prescription data from 75 primary care institutions in Guizhou province, researchers analyzed antibiotic prescriptions for children under 18 in 2020. They evaluated antibiotic appropriateness (including incorrect spectrum, unnecessary use, and combined use of antibiotics) based on guidelines from the National Health Commission of China and the US Centers for Disease Control and Prevention. They also identified potential risk factors for inappropriate use.

During the study period, 155,134 antibiotic prescriptions were written for 143,257 patients. Diseases of the respiratory system accounted for 86.8% of all antibiotic prescriptions (with acute upper respiratory tract infections accounting for 74.9%), followed by diseases of the digestive system (6%) and diseases of skin and subcutaneous tissue (2.1%). The main antibiotic class used was penicillins (63.7%), followed by cephalosporins (18.8%) and lincosamides (5.8%).

Of 137,284 visits analyzed, only 18.3% of antibiotic prescriptions were considered appropriate, and the percentages of unnecessary use, incorrect spectrum of antibiotics, and combined use of antibiotics were 76.9%, 2.4% and 2.4%, respectively. Physicians with lower professional titles and more than 40 years of work duration were relatively more likely to prescribe inappropriate antibiotics.

The study authors say the results suggest it may be necessary to provide a refresher course on antibiotic prescribing for providers in these institutions.

"The inappropriate use of antibiotics in children is still prominent in primary care institutions of southwest China," they wrote. "The education and training of physicians and caregivers in these institutions should be strengthened."

Oct 26 BMC Prim care study

ASP Scan (Weekly) for Oct 28, 2022

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Poor outcomes seen in those with resistant E coli bloodstream infections

Study highlights inappropriate pediatric antibiotic use in China

The study authors say the results suggest it may be necessary to provide a refresher course on antibiotic prescribing for providers in these institutions.

Flu contributing to inappropriate antibiotics for respiratory infections

Originally published by CIDRAP News Oct 26

An analysis of patients in a California health system found relatively high rates of flu-associated prescribing of select antibiotics in certain age-groups, researchers reported today in Epidemiology & Infection.

Researchers with Kaiser Permanente and Harvard T.H. Chan School of Public Health estimated influenza-associated prescribing for five antibiotic classes (macrolides, aminopenicillins, protected aminopenicillins, quinolones, and third-generation cephalosporins) from 2010 through 2018 among patients in the Kaiser Permanente of Northern California health system.

Using data on weekly prescribing counts and weekly rates of respiratory samples positive for influenza A and B, they calculated annual rates of influenza-associated prescribing for the different classes per 100,000 individuals in five age-groups—under 5 years, 5 to 17 years, 18 to 49 years, 50 to 64 years, and over 65 years.

The analysis estimated that 3.4% of all macrolide prescriptions, 2.7% of all aminopenicillin prescriptions, 2.2% of all protected aminopenicillin prescriptions, 3.1% of all third-generation cephalosporin prescriptions, and 1.3% of all quinolone prescriptions were influenza-associated.

Corresponding proportions were higher for certain age-groups. For example, influenza accounted for 4.3% of all macrolide prescriptions in patients 50 and older, 3.3% of all aminopenicillin prescriptions in children under 5, and 5.1%, 5.2%, 4.2%, and 3.4% of aminopenicillin, third-generation cephalosporin, quinolone, and protected aminopenicillin prescriptions in patients aged 5 to 17 years, respectively.

Additionally, the relative contribution of influenza to antibiotic prescribing for any respiratory diagnosis without a bacterial indication in patients over 5 was higher than the corresponding relative contribution to prescribing for any diagnosis.

"Our results suggest a modest benefit of increasing influenza vaccination coverage for reducing antibiotic prescribing for the five studied antibiotic classes, particularly for macrolides in ages over 50y, aminopenicillins in children aged under 18y and 3rd generation cephalosporins in ages over 65y, as well as the potential benefit of other measures to reduce unnecessary antibiotic prescribing for respiratory diagnoses with no bacterial indication in persons aged over 5y, both of which may further contribute to the mitigation of antimicrobial resistance," the study authors wrote.
Oct 26 Epidemiol Infect abstract

Private-sector antibiotic use falls in India, but inappropriate use rises

Originally published by CIDRAP News Oct 26

Private-sector antibiotic consumption fell in India over the previous decade, but rates varied widely across states, with some seeing increased inappropriate use of broad-spectrum antibiotics, researchers reported today in JAC-Antimicrobial Resistance.

Using a nationally representative drug sales audit dataset, researchers with the Public Health Foundation of India and Boston University School of Public Health calculated annual private-sector antibiotic consumption rates from 2011 through 2019 across national, state, and state-group (high focus [HF] and non-high focus [nHF]) levels. They analyzed consumption across different characteristics, including World Health Organization AWaRE (Access, Watch and Reserve) classification, product type, and essentiality.

Overall, the annual consumption rate of private-sector antibiotics decreased by 3.6% from 2011 through 2019, falling from 10.7 defined daily doses per 1,000 persons per day (DIDs) to 10.3 DIDs. But the proportion of Access antibiotics, which are first-line recommended agents, declined (compound annual growth rate [CAGR], -1.7%) while the proportion of Reserve, or last-resort antibiotics, increased (CAGR, 16.8%), and the Access/Watch ratio fell from 0.59 to 0.49, suggesting increased use of broad-spectrum antibiotics.

Analysis of state-level consumption showed that consumption varied widely, with HF states—those states with weak public health infrastructure and indicators—reporting lower overall rates of consumption but increased inappropriate antibiotic use over time, reflected by an increasing consumption of Watch antibiotics and fixed-dose combinations and a significant decline in Access/Watch ratio.

The study authors say the overall decline in private-sector antibiotic consumption could reflect national regulatory reforms that went into effect in 2014. But they note that the increasing consumption of broad-spectrum Watch antibiotics correlates with comparatively higher rates of resistance to these antibiotics in India.

"The rapid decline in Access/Watch ratios in HF states is a serious concern as these states have a considerable population share and they lag in socioeconomic and health indicators," the authors wrote. "The significant variations of inappropriate use at the state level called for state-specific studies to understand the factors—at the health-system, provider and patient level—that drive inappropriate use."
Oct 26 JAC-Antimicrob Resist study